HIV Treatment Flashcards
Who is HIV treatment indicated for?
all individuals diagnosed with HIV
-to reduce morbidity and mortality
-to prevent transmission to sexual partners and infants
especially important for those who have AIDS-defining conditions, acute/recent infection, and individuals who are pregnant
When should HIV treatment be initiated?
initiate as soon as possible
What are the benefits of ARVs?
allows restoration and preservation of immunologic function
reduces HIV-related morbidity & mortality
increases duration and quality of life
prevents transmission
What are some considerations when determining if a patient is ready to start HIV treatment?
ability to take meds consistently
mentally ready?
do they require any supports? (housing, addictions)
provide education around HIV, how the meds will help, adherence, side effects
What is the general MOA of antiretrovirals?
block viral replication within the CD4 cell
-prevents destruction of CD4 cells and allows restoration of immune function
True or false: 1 antiretroviral can achieve and maintain suppression of HIV
false
requires more than 1 antiretroviral to achieve and maintain suppression
What is the MOA of NRTIs?
act as host nucleotide decoys and cause termination of the elongating HIV DNA chain
Describe the process of HIV reverse transcription.
multistep process that results in a copy of linear, double-strand HIV DNA being generated from single strand HIV RNA
during this process of DNA synthesis, the HIV reverse transcriptase incorporates host nucleotides into the elongating primer strand, which is forming opposite to the HIV template strand
What is the MOA of NNRTIs?
bind directly to the HIV reverse transcriptase enzyme and inhibit the function of the enzyme
What must occur for HIV replication to take place?
retroviruses must integrate the linear, double-stranded HIV DNA formed by reverse transcription into the host DNA
What is the role of the HIV enzyme integrase?
3’ processing of the HIV DNA
strand transfer of the HIV DNA into the host DNA
What is the MOA of INSTIs?
currently, available HIV integrase inhibitors utilize multiple mechanisms to block the integrase strand transfer step
-when the HIV integration process is blocked, the HIV DNA becomes a substrate for host repair enzymes that subsequently convert the HIV DNA complex into byproduct
What is the MOA of PIs?
HIV PIs are structurally complex molecules that bind to the active site of HIV protease and inhibit the protease enzyme activity
-disrupt the normal Gag and Gag-Pol polyprotein processing, causing arrest of the normal maturation process, which thereby prevents infection of new cells
What are the four classes of antiretrovirals?
NRTIs
NNRTIs
INSTIs
PIs (almost always boosted)
How many agents are needed for an HIV regimen?
3 active agents from 2 different classes
True or false: monotherapy can be used for HIV
false
monotherapy is never used
Are ritonavir and cobicistat active ARVs?
ritonavir and cobicistat dont count as “active” ARVs
Which drugs are NRTIs?
tenofovir alafenamide
emtricitabine
tenofovir disoproxil fumarate
abacavir
lamivudine
Which drugs are INSTIs?
dolutegravir
bictegravir
elvitegravir/cobicistat
raltegravir
cabotegravir
Which drugs are NNRTIs?
doravirine
rilpivirine
efavirenz
nevirapine
Which drugs are PIs?
darunavir
What is TDF often paired with to form the NRTI backbone of a regimen?
emtricitabine or lamivudine
What are the adverse effects of TDF?
decreased BMD
renal toxicity (decreased GFR, Fanconi Syndrome)
headache
nausea/diarrhea
decreases lipids
severe exacerbation of hepatitis for pts co-infected with HBV/HIV when TDF is d/c
What can increase the risk of renal toxicity with TDF?
combined with a PK booster like ritonavir or cobicistat
What is TAF often combined with to form the NRTI backbone of a regimen?
emtricitabine
What are the adverse effects of TAF?
renal toxicity and decreased BMD
-less likely than TDF
weight gain
headache
nausea/diarrhea
severe exacerbation of hepatitis for pts co-infected with HBV/HIV when TAF is d/c
What is abacavir often paired with to form NRTI backbone of a regimen?
lamivudine
What are the adverse effects of abacavir?
risk of hypersensitivity reaction
potential risk of MI
nausea/diarrhea
What should be checked prior to initiation of abacavir?
HLA-B 5701
-if + = increased likelihood of hypersensitivity rxn which can be fatal
Which patient population might abacavir be seen more commonly in?
infants
-one of few choices
renal patients
What did the REPRIEVE trial show?
past use of abacavir increased the risk of MACE by 50% and current use increased MACE risk by 42%
What is emtricitabine often paired with?
tenofovir (TDF or TAF)
What are the adverse effects of emtricitabine?
minimal toxicity
hyperpigmentation
exacerbation of hepatitis in those co-infected with HBV/HIV who d/c emtricitabine
What is lamivudine often paired with?
abacavir, tenofovir in other countries as part of TLD regimen
What are the adverse effects of lamivudine?
minimal toxicity
exacerbation of hepatitis in those co-infected with HBV/HIV who d/c lamivudine
What are the adverse effects of doravirine?
nausea
dizziness
abnormal dreams
very well tolerated by most and is wt. neutral
How must efavirenz be taken?
at bedtime on an empty stomach
What are the adverse effects of efavirenz?
poorly tolerated
neuropsychiatric symptoms
transaminase elevations
QT prolongation
What are the adverse effects of rilpivirine?
depression
insomnia
headache
QT prolongation
injection site rxn with Cabenuva
What is the dosing issue with nevirapine?
dosed BID after 14 day lead in
-repeat lead in period if d/c more than 7 days
-pts who develop rash continue lead in until rash resolves but do not extend lead in more than 28 days
What are the adverse effects of nevirapine?
rash (including SJS)
symptomatic hepatitis
-more common in females with CD4 > 250, males > 400
Which population might nevirapine be seen in?
babies
-not really used in adults anymore
What are the adverse effects of bictegravir?
really well tolerated
diarrhea/nausea
headache
weight gain
How might dolutegravir be dosed if resistance is present?
may be BID if resistance present
What are the adverse effects of dolutegravir?
more AE than bictegravir
insomnia
headache
depression
weight gain
rare hypersensitivity reactions
What are the adverse effects of cabotegravir?
very well tolerated in most patients
headache
nausea
abnormal dreams
anxiety
insomnia
depression
What are the adverse effects of elvitegravir?
nausea/diarrhea
sleep disturbances
headache
weight gain
What is the main drawback of raltegravir?
dosed BID
What are the adverse effects of raltegravir?
well tolerated
nausea/diarrhea
headache
CK elevation
weight gain
rarely rash
How might darunavir be dosed if resistance is present?
BID if resistance mutations present
How is darunavir always given?
with a PK booster such as ritonavir or cobicistat (CYP 3A4 inhibitors)
What are the adverse effects of darunavir?
tolerability not as good as other ARV regimens
significant GI: diarrhea/nausea
hyperlipidemia
fat maldistribution
implications for CVD
skin rash
hepatotoxicity (not common)
What is the name of the first completely injectable ARV option?
Cabenuva (cabotegravir + rilpivirine)
How is Cabenuva administered?
gluteal IM injection given by HCP every 1 to 2 months
What is unique about Cabenuvas PK?
very long PK tail (implications for resistance if pt d/c)
-can last in body up to 12 months
- low [ ] = perfect env for virus to develop resistance
Describe the suitability for the Cabenuva injection.
no known or suspected mutations to cabo or rilp
no evidence of chronic HBV
CrCl > 30 ml/min
no signs of liver failure (Child Pugh C)
not pregnant or planning pregnancy
virally suppressed before first injection (6 mo or greater)
pt able to commit to regular injections
pt has reliable contact info
What are the significant drug interactions with Cabenuva?
anticonvulsants (CBZ, OxCBZ, PHT, PHB)
antimycobacterials
dexamethasone ( > 1 dose)
St Johns Wort
What are the recommended regimens for individuals with no history of using CAB-LA as PrEP?
BIC/TAF/FTC (Biktarvy)
DTG plus (TAF or TDF) plus (FTC or 3TC)
DTG/3TC*
Which patients should not use DTG/3TC as their regimen?
HIV RNA > 500,000 copies/ml
HBV coinfection
ART to be started before results of HIV genotypic resistance testing
What should occur before starting ART for patients who have a history of CAB-LAB use as PrEP?
INSTI genotype resistance testing should be performed before starting ART
Which regimens are used if ART is to be started before results of genotypic testing?
DRV/c or DRV/v with (TAF or TDF) plus (FTC or 3TC)
What is a rapid start?
starting ARV within days up to 2 weeks from when patient is diagnosed
What are the benefits of rapid initiation?
earlier linkage to care
higher rates of retention in care
higher rates of suppression and shorter time to suppression
health benefits to the patient
reduces onward transmission
Which regimens are typically used for rapid start?
Biktarvy or Truvada + Tivicay
less often consider Truvada + boosted PI (darunavir/cobicistat or ritonavir)
takes approx 6 wks to get genotype results back, these regimens have a low likelihood of resistance if pt happened to have transmitted resistance
Which class should not be used for rapid start in if the pt has been on CAB-LA for PrEP?
INSTI
-do not use if have been on CAB-LA for PrEP until genotype results back
What are lab values that should be obtained at baseline?
resistance testing
CD4
HIV VL
HLA-B 5701
HAV & HBV serology
HCV screening
toxo serology
TB screening
CBC
SCr
PO4
liver enzymes
lipids
random glucose
U/A
pregnancy test
What are some important patient characteristics that need to be known before initiating ART?
comorbidities
-CV, renal, hepatic, psychiatric, osteoporosis
-OIs
other medications (DDIs)
pregnancy/child-bearing age
social factors
How often should VL be taken?
4-6 weeks after initiating ARV or after switching
then q 3-6 months
How often should CD4 be taken?
q 3-6 months
-if consistent adherence and suppressed, can lengthen to q 12 months
-if CD4 > 500, CD4 monitoring is optional now (after 2 yrs with suppressed VL)
True or false: most of the new regimens are very well tolerated
true
pt may not have any AE at all
Which AE is common in the first few days of initiating ARV?
GI upset but often self-resolving
Which side effects are most commonly reported by patients?
GI and psych
Which antiretrovirals have cardiac conduction abnormality AEs?
rilpivirine
efavirenz
Which antiretrovirals have CVD AEs?
abacavir
boosted darunavir
Which antiretrovirals impact BMD?
TDF > than other NRTIs (TAF alt to TDF, minimizes decreased BMD)
all ARV regimens have some decrease
Which antiretrovirals can cause dyslipidemia?
TAF
abacavir
efavirenz
all boosted PI
elvitegravir
TDF lipid suppressive effect
Which antiretrovirals can cause hepatotoxicity?
efavirenz
nevirapine
PIs
dolutegravir
Which antiretrovirals can cause hypersensitivity reactions?
abacavir (HLA-B 5701)
nevirapine
Which antiretrovirals can cause psychiatric effects?
efavirenz
rilpivirine
dolutegravir
doravirine
Which antiretrovirals can impact renal function?
TDF
-increased risk with boosted regimens
Which antiretrovirals can cause weight gain?
INSTIs more than other ARVs
some indication TAF has small increase in wt
What are some ways that side effects of ARVs can be managed?
nausea - can try Gravol or ondansetron
diarrhea - can try Metamucil to bulk stool or Imodium
headache - prescribe acetaminophen, ibuprofen, naproxen
-caution using NSAIDs with TDF esp in boosted regimens
if suspected AE will be ongoing or contribute to comorbid conditions, refer back to an HIV specialist for consideration of a change in ARV regimen
What is the major factor in ensuring virologic success and a significant determinant of survival?
adherence
What are some ways to check for adherence to ARVs?
ask pt (non-judgementally)
check PIP fill history
talk to community pharmacy
touch base with HIV care team
What are the factors associated with poor adherence to ARVs?
active alcohol or drug use
competing priorities
depression
lack of social support
low literacy
advanced HIV infection
young age
What are the reasons for non-adherence to ARVs?
experiencing AE (or attributing sx to ARVs)
regimen too complex (++ pills)
forgetting to take medication
oversleeping and missing a dose
being away from home
not understanding importance of adherence
concerns around confidentiality
active substance abuse
mental health challenges
social issues
cost
What are some strategies that can be implemented to improve adherence to ARVs?
bubble packing
weekly pill organizer
place medication near something pt does everyday
set an alarm, utilize apps
ask family members/friends to remind pt
plan ahead for changes in routine (i.e. travel)
keep back-up supply in purse/backpack
set up auto refills with community pharmacy
pair methadone fills with ARVs
keep clinic appointments with care team
What causes HIV drug resistance?
changes in the genetic structure of HIV that affect the ability of drugs to block the replication of the virus
What are the types of resistance?
transmitted resistance:
-when a person acquires a strain of HIV that is already resistant ARV drugs
acquired resistance:
-when a drug-resistant strain of HIV emerges while a person is taking ARV therapy
Describe the process for how HIV drug resistance develops.
- HIV begins to to multiply (billions of virions daily)
- HIV drugs block replication and reduce VL
- person stops taking ARVs regularly & virus multiplies again, possibility of virus mutating
- new mutant virus does not respond to previous drugs to block replication, resulting in resistance
- person must change ARVs to effectively block replication
- adherence is key to prevent mutations of the virus and prevent production of drug-resistant HIV
What does it mean if the HIV is wild-type?
no resistance mutations
-most susceptible to ARVs
What are the 3 factors that may contribute to suboptimal levels of drug?
adherence
malabsorption
drug-drug interactions
How many viral copies are needed to detect drug resistance mutations in relevant viral genes?
500-100 viral copies (minimum 250 copies)
What is a genetic barrier to resistance?
a high genetic barrier to resistance allows a medication to bind itself tightly to the virus and keeps working even if the virus has changed
-while some medications become less effective after the virus changes once, those with a high genetic barrier to resistance may continue to work even after several changes occur
What is virologic suppression?
HIV RNA level below the LLOD of the assay
What is virologic failure?
inability to achieve or maintain suppression of viral replication to < 200 copies/ml
What is incomplete virologic response?
two consecutive HIV RNA levels > 200 copies/ml after 24 weeks on an ARV regimen in a patient who hasnt had documented virologic suppression on that regimen
What is a virologic blip?
after being suppressed, an isolated detectable HIV RNA level that returns to suppression
What is low-level viremia?
confirmed detectable HIV RNA level < 200 copies/ml
Match the CD4 count to the opportunistic infection.
tuberculosis at any CD4
CD4 < 200:
-Pneumocystis pneumonia
-oropharyngeal Candidiasis
CD4 < 100:
-Cryptococcal pneumonia and meningitis
-Toxoplasmosis
-esophageal Candidiasis
CD4 < 50:
-disseminated MAC
-CMV retinitis
Which OI is most common?
oropharyngeal Candidiasis
What is the preferred treatment for oropharyngeal Candidiasis?
oral fluconazole 100 mg/day x 7-14 days
When should esophageal Candidiasis be suspected in an HIV patient?
anyone with a low CD4 count and dys/odynophagia
What is the preferred treatment for esophageal Candidiasis?
oral fluconazole 100-400 mg/day x 14-21 days
-topical nystatin alone should not be used
-empiric therapy reasonable if clinical suspicion
True or false: absence of oropharyngeal Candidiasis rules out esophageal
false
What causes Pneumocystis pneumonia?
Pneumocystis jirovecii
-fungi
How is Pneumocystis jirovecii spread?
airborne spread
-asymptomatic if normal immune system
How does Pneumocystis pneumonia present?
typically presents in immunocompromised hosts as a subacute onset syndrome of dry cough, fever, exertional dyspnea, chest discomfort and even respiratory failure
-can have hypoxemia and elevated LDH
What would be seen on a CXR for a patient with Pneumocystis pneumonia?
diffuse, bilateral, interstitial infiltrates, rarely pneumatoceles/pneumothorax
How is Pneumocystis pneumonia diagnosed?
microscopic demonstration of the organism
Which patients should receive PCP prophylaxis?
CD4 count < 200 cells/mm3 or < 14%
Which agent is used for PCP prophylaxis?
TMP/SMX
-1 DS tab daily or 1 SS daily (or 3x/wk but uncommon)
In addition to covering for PCP, what else will TMP/SMX cover?
1 DS daily provides cross coverage for Toxoplasmosis (if Ab+ and CD4 < 100) and other bacterial infections
What are some alternative options for PCP prophylaxis?
dapsone
aerosolized pentamidine
less commonly atovaquone, dapsone+pyremethamine+leucovorin
When should primary PCP prophylaxis be discontinued?
when CD4 over 200 cells/mm3 x 3 months or in some cases where CD4 100-200 cells/mm3 and pt is suppressed
How is PCP treated?
Septra DS 2 tabs po q8h x 21 days for mild-moderate
or 15-20 mg of TMP component/kg/day IV q6-8h x 21 days for moderate to severe
-can switch to oral after improvement
What should occur after a patient has been treated for PCP?
secondary prophylaxis should begin
What should be checked prior to dapsone use?
G6PD
What causes MAC?
Mycobacterium avium complex
-ubiquitous in environment
How does MAC present?
as a disseminated disease with malaise/fever/weight loss/diarrhea/lymphadenopathy/abdominal pain
hepatosplenomegaly common
clues: severe anemia, elevated ALP
How is MAC diagnosed?
Myco F/lytic blood cultures
tissue cultures
Which patients should be started on MAC prophylaxis?
people with CD4 counts < 50 cells/mm3 and not on ARVs or who remain viremic despite ARV therapy
-prophylaxis not recommended in those starting ARV therapy and expected to suppress, regardless of CD4 count
Which agent is used for MAC prophylaxis?
azithromycin 1250 mg po once weekly
-MAC blood cultures prior to initiating proph to rule out active infection
What is the treatment for MAC?
two or more antimycobacterial drugs
-prevents resistance from developing
1. clarithromycin 500 mg po BID (alt: azithromycin)
2. ethambutol 15 mg/kg/day
3. rifabutin 300 mg q 24h
3 or 4 drugs considered when CD4 < 50, high mycobacterial load, absence of effective ART
How long should MAC be treated for?
maintain treatment for 12 months and until CD4 is > 100 x 6 months
What is IRIS?
exaggerated inflammatory reaction to a disease-causing microorganism that can occur when the immune system starts to recover following initiation of ARVs
-unmasking IRIS: refers to a flare-up of previously undiagnosed infection soon after ARVs are started
-paradoxical IRIS: refers to the worsening of a previously diagnosed infection after ARVs are started
can be mild or life-threatening
When is IRIS most often seen?
in first 8 weeks of ARV therapy in pts with advanced HIV
In which patients do most cases of IRIS occur in?
low CD4 counts and high viral loads
What is the treatment for IRIS?
mild: NSAIDs, symptomatic tx, OI tx
severe: steroids, interruption in ARVs in severe steroid-refractory cases
What are some common drug interactions with ARVs?
TB meds (esp rifampin)
acid reducers (PPIs, H2RAs, antacids)
anticoagulants, antiplatelets
statins
anticonvulsants
antidepressants, anxiolytics, antipsychotics
steroids all routes
alpha antagonists
rule of thumb: if see cobicistat or ritonavir –> think DDI
